BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact

We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it h...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-10, Vol.105 (40), p.15517-15522
Main Authors: Scholz, Jean L, Crowley, Jenni E, Tomayko, Mary M, Steinel, Natalie, O'Neill, Patrick J, Quinn, William J. III, Goenka, Radhika, Miller, Juli P, Cho, Yun Hee, Long, Vatana, Ward, Chris, Migone, Thi-Sau, Shlomchik, Mark J, Cancro, Michael P
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antibody Formation - immunology
Antigens
B lymphocytes
B-Cell Activating Factor - antagonists & inhibitors
B-Cell Activating Factor - metabolism
B-Cell Activating Factor - physiology
B-Lymphocytes - cytology
B-Lymphocytes - immunology
Biological Sciences
Cells
Cytokines
Female
Immunity, Innate - immunology
Immunization
Immunoglobulins
Immunologic Memory - immunology
Isotypes
Memory
Mice
Mice, Inbred C57BL
Plasma
Plasma cells
Receptors
Spleen
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Summary:We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not, although both were more resistant than naïve cells. There was also heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secreting cells remained constant. Together, these findings show that memory B cells and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be separately manipulated.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0807841105